Prostaglandin D2 induces heme oxygenase-1 mRNA expression through the DP2 receptor.
Prostaglandin (PG) D(2) exerts multiple actions through interaction with distinct receptors, DP1 and DP2. We have shown that PGD(2) induces the expression of heme oxygenase-1 (HO-1) in the retinal pigment epithelium (RPE) that is essential for survival of photoreceptors. HO-1 is a key enzyme in physiological heme degradation. Here, we explored the mechanism for the PGD(2)-mediated induction of HO-1 expression using ARPE-19 human RPE cells. ARPE-19 cells secrete PGD(2) and express DP2 mRNA, but not DP1 mRNA. Treatment with a DP2 agonist, 15(R)-15-methyl-PGD(2) or DK-PGD(2), increased HO-1 mRNA expression, and pretreatment with a DP2 antagonist, CAY10471, decreased the magnitude of the PGD(2)-mediated HO-1 induction. By contrast, either DP1 agonist or antagonist caused only marginal influence on HO-1 expression. Moreover, transient expression assays showed the DP2 agonist activated the HO-1-gene promoter in the enhancer-dependent manner. Thus, PGD(2) induces HO-1 mRNA expression through DP2 receptor, linking the PGD(2)-DP2 signaling with heme homeostasis.
Satarug
Soisungwan
S
Department of Molecular Biology and Applied Physiology, Tohoku University School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, Japan.
Wisedpanichkij
Raewadee
R
Takeda
Kazuhisa
K
Li
Bin
B
Na-Bangchang
Kesara
K
Moore
Michael R
MR
Shibahara
Shigeki
S
D002104:Cadmium / Q000494:pharmacology; D002227:Carbazoles / Q000494:pharmacology; D002460:Cell Line; D006418:Heme / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000096:biosynthesis*; D006706:Homeostasis; D006801:Humans; D011401:Promoter Regions, Genetic / Q000187:drug effects; D015230:Prostaglandin D2 / Q000494:pharmacology / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D011971:Receptors, Immunologic / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011982:Receptors, Prostaglandin / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D055213:Retinal Pigment Epithelium / Q000187:drug effects / Q000201:enzymology*; D013449:Sulfonamides / Q000494:pharmacology
C533609:CAY 10471; D002227:Carbazoles; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; D013449:Sulfonamides; D002104:Cadmium; D006418:Heme; D051547:Heme Oxygenase-1; D015230:Prostaglandin D2; C036293:prostaglandin D2 receptor